P. Gionchetti et al., BIOAVAILABILITY OF SINGLE AND MULTIPLE DOSES OF A NEW ORAL FORMULATION OF 5-ASA IN PATIENTS WITH INFLAMMATORY BOWEL-DISEASE AND HEALTHY-VOLUNTEERS, Alimentary pharmacology & therapeutics, 8(5), 1994, pp. 535-540
Aims: An oral multiparticulate coated formulation of 5-aminosalicylic
acid (5-ASA; mesalazine) has been developed to provide a controlled re
lease of the drug, in a pH-dependent fashion, in the distal ileum and
colon. The purpose of the present study was to assess the systemic ava
ilability of the drug and its metabolite, acetyl-5-ASA, following sing
le (800 mg) and multiple (2400 mg for 56 days) oral dose administratio
n. Methods: Three groups were investigated: six healthy volunteers, si
x patients with ulcerative colitis, and nine patients with Crohn's dis
ease in remission. In the single oral dose study (800 mg) ail three gr
oups participated, whereas in the multiple oral dose study (2400 mg/da
y for 56 days) only the patients with inflammatory bowel disease took
part. Plasma and urine 5-ASA and Ac-5-ASA were measured for 48 h. Resu
lts: In the single oral dose regimen, systemic absorption of 5-ASA and
Ac-5-ASA were low and did not differ between the three groups. Only a
bout 20% of the 5-ASA given was absorbed, with more than 80% of the dr
ug being available in the terminal ileum and colon for therapeutic act
ivity. The multiple oral dose regimen in patients with inflammatory bo
wel disease produced a significantly higher plasma concentration and u
rine excretion of both 5-ASA and Ac-5-ASA by the end of the treatment,
in comparison to the first dose. There was a statistically higher sys
temic absorption of 5-ASA in patients with ulcerative colitis than in
patients with Crohn's disease. After 56 days of dosing, no adverse eve
nt was reported and laboratory screening tests remained within normal
ranges. Conclusions: The new oral 5-ASA formulation is gradually relea
sed throughout the small and large intestine, reflected by a low plasm
a concentration of the drug and its metabolite, with about 80% of the
drug being available for ileum-colon therapeutic activity.